Alkyl halides, super hydrogen production and the pathogenesis of pneumatosis cystoides coli

Abstract

Background and aims-The colons of patients with pneumatosis cystoides coli produce excessive H 2. Exposure to alkyl halides could explain this. Six consecutive patients who had pneumatosis cystoides coli while taking chloral hydrate (1-5+ g/day) are reported. Patients 2 and 3 were investigated after they had ceased chloral hydrate treatment. One produced methane, the other did not. (Pneumatosis cystoides coli patients are non-methanogenic according to the literature.) Both had overnight fasting breath H 2 of less than 10 ppm. A literature review disclosed just one patient who was using chloral at the time of diagnosed pneumatosis cystoides coli, but an epidemic of the disease in workers exposed to trichloroethylene. Methods-(i)In vitro experiments with human faeces: chloral or closely related alkyl halides were added to anaerobic faecal cultures derived from four methaneproducing and three non-methanogenic human subjects. H 2 and CH 4 gases were measured. (ii) In vivo animal experiment: chloral hydrate was added to drinking water of four Wistar rats, and faecal H 2 compared with control rats. Results-Alkyl halides increased H 2 up to 900 times in methanogenic and 10 times in non-methanogenic faecal cultures. The K i of chloral was 0.2 mM. Methanogenesis was inhibited in concert with the increase in net H 2 . In the rat experiment, chloral hydrate increased H 2 10 times, but did not cause pneumatosis. Conclusions-Chloral and trichloroethylene are alkyl halides chemically similar to chloroform, a potent inhibitor of H 2 consumption by methanogens and acetogens. These bacteria are the most important H 2 -consuming species in the colon. It is postulated that exposure to these alkyl halides increases net H 2 production, which sets the scene for "counterperfusion supersaturation" and the formation of gas cysts. In recent times, very low prescribing rates for chloral have caused primary pneumatosis cystoides to become extremely rare. As with primary pneumatosis, secondary pneumatosis cystoides, which occurs if there is small bowel bacterial overgrowth distal to a proximally located gut obstruction, is predicted by counterperfusion supersaturation. "Inherent unsaturation" due to metabolism of O 2 is a safety factor, which could explain why gas bubbles do not form more often in tissue with high H 2 tension. (Gut 1997; 41: 778-784)

The Spectrum of Pneumatosis Intestinalis

“…Direct gas diffusion across the mucosa because of a gradient between intraluminal and serum partial pressures is an intriguing theory of causality. 80,104 Patients with PI have been shown to have abnormally high levels of hydrogen in their pneumocysts. 87,105,106 This led to the theory of "counterperfusion supersaturation," whereby colonic bacteria produce hydrogen tensions that exceed nitrogen tension in blood, leading to a hydrogen diffusion gradient toward the submucosal vessels.…”

“…62 This theory has been supported experimentally in rats and in some patients with primary PI due to the ingestion of alkyl halides (chloral hydrate and trichloroethylene). 80 Ingestion of alkyl halides as inciting agents for PI has been sup-ported by case reports and epidemiologic studies. [78][79][80][81] Metabolism of oxygen decreases gas tension in tissues.…”

A rare cause of abdominal compartment syndrome: acute trichlorethylene overdose

“…The connection between TCE ingestion and ACS remains speculative but could be inferred from experimental data on the pathophysiology of pneumatosis cystoides coli (11). TCE exposure is known to limit the metabolism of hydrogenconsuming colonic bacteria, which leads to a massive increase in hydrogen tension in the gut lumen and thereby to acute gut distension.…”

Pneumatosis Intestinalis Presenting as Small Bowel Obstruction without Bowel Ischemia after Mechanical Ventilation

“…The first component is the mechanical aspect of gas traversing the mural portion Case Reports in Medicine 3 of the bowel. This can be precipitated by microbreaks in the mucosa, such as those caused by inflammation or necrosis; it can also be the result of direct gas diffusion across an intact mucosal membrane, as can occur in instances of increased transabdominal pressure [6,7]. The second aspect is the origin of the gas; while some amount of intramural gas is normally present in the human bowel, bacterial overgrowth and invasion of the bowel wall can result in excess gas production favoring the formation of PI [8].…”